Richardson R Mark, Kells Adrian P, Martin Alastair J, Larson Paul S, Starr Philip A, Piferi Peter G, Bates Geoffrey, Tansey Lisa, Rosenbluth Kathryn H, Bringas John R, Berger Mitchel S, Bankiewicz Krystof S
Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Stereotact Funct Neurosurg. 2011;89(3):141-51. doi: 10.1159/000323544. Epub 2011 Apr 14.
BACKGROUND/AIMS: A skull-mounted aiming device and integrated software platform has been developed for MRI-guided neurological interventions. In anticipation of upcoming gene therapy clinical trials, we adapted this device for real-time convection-enhanced delivery of therapeutics via a custom-designed infusion cannula. The targeting accuracy of this delivery system and the performance of the infusion cannula were validated in nonhuman primates.
Infusions of gadoteridol were delivered to multiple brain targets and the targeting error was determined for each cannula placement. Cannula performance was assessed by analyzing gadoteridol distributions and by histological analysis of tissue damage.
The average targeting error for all targets (n = 11) was 0.8 mm (95% CI = 0.14). For clinically relevant volumes, the distribution volume of gadoteridol increased as a linear function (R(2) = 0.97) of the infusion volume (average slope = 3.30, 95% CI = 0.2). No infusions in any target produced occlusion, cannula reflux or leakage from adjacent tracts, and no signs of unexpected tissue damage were observed.
This integrated delivery platform allows real-time convection-enhanced delivery to be performed with a high level of precision, predictability and safety. This approach may improve the success rate for clinical trials involving intracerebral drug delivery by direct infusion.
背景/目的：已开发出一种用于磁共振成像（MRI）引导的神经介入手术的头戴式瞄准装置和集成软件平台。鉴于即将开展的基因治疗临床试验，我们对该装置进行了改进，以通过定制设计的输注套管进行治疗药物的实时对流增强递送。在非人灵长类动物中验证了该递送系统的靶向准确性和输注套管的性能。
将钆特醇输注到多个脑靶点，并确定每个套管放置的靶向误差。通过分析钆特醇分布和对组织损伤进行组织学分析来评估套管性能。
所有靶点（n = 11）的平均靶向误差为0.8毫米（95%置信区间 = 0.14）。对于临床相关体积，钆特醇的分布体积随输注体积呈线性函数增加（R² = 0.97）（平均斜率 = 3.30，95%置信区间 = 0.2）。任何靶点的输注均未产生阻塞、套管反流或相邻通道渗漏，且未观察到意外组织损伤的迹象。
这种集成递送平台能够以高度的精确性、可预测性和安全性进行实时对流增强递送。这种方法可能会提高涉及通过直接输注进行脑内药物递送的临床试验的成功率。
